Neoadjuvant systemic therapy for inoperable differentiated thyroid cancers: Impact on tumor resectability.

BACKGROUND: Limited treatment options exist for inoperable thyroid cancers. We evaluated whether neoadjuvant use of systemic tyrosine kinase inhibitors facilitates surgery of differentiated thyroid cancers in this challenging context. METHODS: A single-institution experience of 42 patients receiving tyrosine kinase inhibitors for papillary, follicular and anaplastic thyroid carcinomas between 2018 and 2023 was reviewed to identify differentiated thyroid cancers treated with neoadjuvant tyrosine kinase inhibitors (dabrafenib/trametinib, lenvatinib/pembrolizumab, or lenvatinib alone) via multidisciplinary protocols. RESULTS: Nine patients with differentiated thyroid cancers (age 49 years, range 19-80, 5 women, 4 men) received neoadjuvant tyrosine kinase inhibitors with intent to improve resectability of primary or recurrent/residual tumors. All had locoregionally advanced disease deemed either unresectable or resectable with unacceptable morbidities. Six exhibited distant metastases (6 lungs, 6 vertebral/axial bones, 1 sternum). Tumors had BRAF V600E (6 papillary thyroid carcinoma) or RAS/TERT (2 follicular thyroid carcinoma) mutations or NCOA4-RET fusion. Most received neoadjuvant tyrosine kinase inhibitors for <6 months with visible results within weeks, radiologically and by examination. All patients completing surgery achieved R0 resection without major surgical complications or aerodigestive structure resection. Neoadjuvant tyrosine kinase inhibitors were generally well-tolerated (4 minor, 1 major toxicity that halted therapy but not surgery). Unique patients with distant metastases continued to receive adjuvant tyrosine kinase inhibitors. At median postoperative follow-up of 2 years, all patients are alive without new locoregional recurrence. CONCLUSION: Neoadjuvant use of tyrosine kinase inhibitors seems extremely effective in downstaging surgically unresectable differentiated thyroid cancers to achieve R0 resection while avoiding unnecessary surgical morbidities. A multidisciplinary approach with early genomic profiling to guide personalized neoadjuvant use of tyrosine kinase inhibitors is essential. Prospective studies are urgently needed to define the potential role of neoadjuvant tyrosine kinase inhibitors in advanced thyroid cancer management.

Addressing Falls Among Older Oncology Patients Through Complexity Science.

Traditional quality assurance processes provide significant opportunities for positive disruption. Doctor of Nursing Practice (DNP) students are well positioned to apply program learning to large-scale change in complex organizations. This article presents an innovative approach for creating a point-of-care interdisciplinary approach to address high fall risk frequencies in ambulatory oncology clinics using complexity leadership principles. Processes for nurse executives to consider for replication of this approach for other challenging clinical situations are suggested using the emerging competence of DNP educated nurses. Adults with cancer who are older than 65 years are at a higher risk for falls than older adults without cancer. Oncology providers and nurses are not routinely screening, documenting, and preventing falls. A fall injury in an older adult with cancer may not only delay or impact cancer treatment but also result in hospitalization, loss of function, and/or death. Increasing awareness of the impact of falls and implementing change within a large ambulatory health care organization requires an interdisciplinary team approach. Complexity theory supports nonlinear change initiated at the grassroots level to create a dynamic movement to bring forth emergence and adaptation. The use of the Centers for Disease Control and Prevention STEADI (Stopping Elderly Accidents, Deaths, and Injuries) initiative will enable oncology professionals to screen, assess, and intervene by collaborating, communicating, and coordinating with other health care specialists to introduce a fall prevention quality improvement system process. Nurse executives need to know about STEADI.

Multidisciplinary Team Planning for Patients with Head and Neck Cancer.

The multidisciplinary team planning conference is critical in the evaluation and management of patients with head and neck cancer. The management is complex and dictates the care of a multidisciplinary team for optimal results. First, the head and neck multidisciplinary team ensures the complete evaluation of patients before beginning treatment. Second, the team improves the accuracy of diagnosis and staging on which to base the most appropriate treatment. Third, the team improves the outcomes of treatment by appealing to the best available evidence, by following clinical practice guidelines and treatment algorithms, and by engaging in clinical research trials.

Cervical tracheal transection after scarf entanglement in a go-kart engine.

BACKGROUND: Tracheal disruption secondary to blunt force occurs infrequently. Most individuals suffering such an injury die before arriving at a hospital. Diagnosis for those who do present alive is often delayed, as signs and symptoms typically do not match the severity of injury. OBJECTIVE: The objectives of this case report are to present a unique mechanism for tracheal disruption and to discuss our management strategy. CASE REPORT: We describe an 18-year-old man who suffered tracheal disruption after entanglement of his scarf in a go-kart engine. His initial workup was conducted by emergency physicians and included computed tomographic evaluation of the neck. After diagnosis, the patient was transported to an operating suite. Awake tracheostomy was performed in this controlled environment to secure the airway, after which the trachea was repaired via primary anastomosis. CONCLUSIONS: Prompt recognition and appropriate intervention are critical in the care of patients with suspected tracheal transection to prevent mortality.

Quality indicators in head and neck operations: a comparison with published benchmarks.

OBJECTIVE: To investigate the reproducibility of quality indicators in the care of patients undergoing operations for head and neck cancer. DESIGN: A review of specialty-specific surgical quality indicators in a cohort undergoing procedures for definitive treatment of head and neck cancer, stratified by high and low acuity of the surgical procedures and compared with established benchmarks. SETTING: A large tertiary care institution and an associated multidisciplinary cancer center. PATIENTS: Fifty randomly selected patients with evaluable data who were diagnosed as having head and neck cancer that was definitively treated using any of the 3 modalities (surgical procedures, chemotherapy, and/or radiotherapy) during a 15-month period at our center. Twenty-one patients who underwent operations form the basis of this report. MAIN OUTCOME MEASURES: Procedures were stratified by acuity on the basis of the extent of the operation. Data were centered on quality indicators designed to reflect length of stay, readmission within 30 days postoperatively, return to the operating room within 7 days of surgery, use of blood products, 30-day mortality, adequacy of reports on surgical pathologic findings, and surgical site infection. RESULTS: Diagnoses in the cohort included carcinoma of the oral cavity in 19 patients (39%), oropharynx in 14 (29%), larynx in 13 (27%), and hypopharynx in 3 (6%). High- and low-acuity surgical procedures were performed in 12 and 7 patients, respectively. No statistically significant differences in the measures for quality indicators were found between the cohort and the calculated benchmarks. CONCLUSION: Our findings demonstrate the applicability of quality indicators to the care of patients with head and neck cancer treated by surgical intervention stratified by acuity and compared with established benchmarks.

Outcomes after definitive treatment for cutaneous angiosarcoma of the face and scalp.

BACKGROUND: The aim of the present analysis was to retrospectively evaluate outcomes in patients with cutaneous angiosarcoma of the face/scalp treated curatively with surgery, radiation therapy (RT), or a combination of surgery and RT. METHODS: In all, 70 patients with nonmetastatic angiosarcoma underwent surgery, RT, or combined-modality therapy. Of these, 20 patients (29%) were treated with surgery alone, 27 patients (39%) with RT alone, and 23 patients (33%) with combined-modality therapy; 44 patients received chemotherapy, either neoadjuvantly or adjuvantly or both. RESULTS: Median follow-up was 2.1 years. The overall survival (OS) rate was 43% at 5 years, and disease-specific survival (DSS) was 46% at 5 years. Tumor size > 5 cm and satellitosis were prognostic for inferior OS and DSS. Combined-modality therapy (vs surgery alone or RT alone) was associated with improved OS, DSS, and local control. CONCLUSIONS: Primary local therapy with combined-modality therapy was associated with improved local control, OS, and DSS for patients with angiosarcoma of the face/scalp.

Approach and safety of comprehensive central compartment dissection in patients with recurrent papillary thyroid carcinoma.

BACKGROUND: Despite the generally favorable prognosis of patients with papillary thyroid cancers, 10-year recurrence rates for patients with stage I to III disease is greater than 20%, with central compartment recurrences common among these recurrent sites. METHODS: This study is a retrospective analysis of consecutive patients treated by a single surgeon over an 18-month period of time terminating in 2003. RESULTS: Sixty-three patients underwent a comprehensive dissection of levels VI and VII for papillary thyroid carcinoma during this period. There was a female predominance of 2:1, with 48% of patients being greater than 45 years of age. The median number of lymph nodes identified was 16 (range, 3-52), with 7 (1-20) lymph nodes pathologically involved. Permanent hypoparathyroidism was present on presentation in 13% of patients and developed in an additional 5% following surgery. Although recurrent laryngeal paralysis was present on presentation among 8 (13%) of patients, no patients experienced paralysis of documented functioning recurrent laryngeal nerves or necessitated tracheotomy. Postoperative thyroglobulin levels were reduced to nondetectable in 71% of the informative cases. Over 60% of patients were discharged on their first postoperative day. CONCLUSION: Bilateral paratracheal and superior mediastinal dissection is an oncologically safe procedure exhibiting minimal morbidity when performed among experienced individuals despite multiple prior surgical procedures or existing vocal cord paralysis.

Sarcomas of the head and neck region.

Sarcomas of the head and neck are a heterogeneous group of rare malignancies with highly variable clinical presentation, pathologic classification, and biologic behavior. Managing patients with sarcoma is a formidable challenge for surgical, medical, and radiation oncologists. This article reviews current approaches in patient evaluation, staging, prognosis, and treatment, with emphasis on prolonged survival and quality of life.

High rate of BRAF and RET/PTC dual mutations associated with recurrent papillary thyroid carcinoma.

PURPOSE: Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, usually possesses BRAF mutation or rearranged in translation (RET)/PTC rearrangements. PTC usually possesses BRAF mutation or RET/PTC rearrangements. The mutation status of patients with recurrent PTC has never been characterized in a large population. EXPERIMENTAL DESIGN: Mutation status was determined in a cohort of 54 patients with recurrent PTC and analyzed for clinicopathologic relationships. BRAF and ras mutations were determined by PCR and sequencing of genomic DNA. RET/PTC rearrangements were analyzed by reverse transcription-PCR. RESULTS: BRAF mutation in exon 15 (V600E) was found in 42/54 (77.8%) recurrent PTC patients. The RET/PTC rearrangements were detected in 9 of 54 (16.7%) patients. In addition, 5 of 54 (9.3%) recurrent PTC patients had both a BRAF mutation and a RET/PTC rearrangement. The prevalence of tumors with dual mutations found in the recurrent population far exceeds the frequency historically reported for patients with primary PTC. Patients with dual mutations were significantly older (80% older than 45 years) than patients with a BRAF mutation alone (38% older than 45 years). CONCLUSIONS: Recurrent PTC is significantly associated with a predominant BRAF mutation. RET/PTC rearrangements, although commonly associated with primary PTCs in younger patients, are uncommonly found in recurrent PTC patients. In addition, the incidence of dual mutations was higher in patients with recurrent PTC than in those primary PTC, as reported by others.

Evaluation of geometric changes of parotid glands during head and neck cancer radiotherapy using daily MVCT and automatic deformable registration.

BACKGROUND AND PURPOSE: To assess and evaluate geometrical changes in parotid glands using deformable image registration and megavoltage CT (MVCT) images. METHODS: A deformable registration algorithm was applied to 330 daily MVCT images (10 patients) to create deformed parotid contours. The accuracy and robustness of the algorithm was evaluated through visual review, comparison with manual contours, and precision analysis. Temporal changes in the parotid gland geometry were observed. RESULTS: The deformed parotid contours were qualitatively judged to be acceptable. Compared with manual contours, the uncertainties of automatically deformed contours were similar with regard to geometry and dosimetric endpoint. The day-to-day variations (1 standard deviation of errors) in the center-of-mass distance and volume were 1.61mm and 4.36%, respectively. The volumes tended to decrease with a median total loss of 21.3% (6.7-31.5%) and a median change rate of 0.7%/day (0.4-1.3%/day). Parotids migrated toward the patient center with a median total distance change of -5.26mm (0.00 to -16.35mm) and a median change rate of -0.22mm/day (0.02 to -0.56mm/day). CONCLUSION: The deformable image registration and daily MVCT images provide an efficient and reliable assessment of parotid changes over the course of a radiation therapy.

Assessment of parotid gland dose changes during head and neck cancer radiotherapy using daily megavoltage computed tomography and deformable image registration.

PURPOSE: To analyze changes in parotid gland dose resulting from anatomic changes throughout a course of radiotherapy in a cohort of head-and-neck cancer patients. METHODS AND MATERIALS: The study population consisted of 10 head-and-neck cancer patients treated definitively with intensity-modulated radiotherapy on a helical tomotherapy unit. A total of 330 daily megavoltage computed tomography images were retrospectively processed through a deformable image registration algorithm to be registered to the planning kilovoltage computed tomography images. The process resulted in deformed parotid contours and voxel mappings for both daily and accumulated dose-volume histogram calculations. The daily and cumulative dose deviations from the original treatment plan were analyzed. Correlations between dosimetric variations and anatomic changes were investigated. RESULTS: The daily parotid mean dose of the 10 patients differed from the plan dose by an average of 15%. At the end of the treatment, 3 of the 10 patients were estimated to have received a greater than 10% higher mean parotid dose than in the original plan (range, 13-42%), whereas the remaining 7 patients received doses that differed by less than 10% (range, -6-8%). The dose difference was correlated with a migration of the parotids toward the high-dose region. CONCLUSIONS: The use of deformable image registration techniques and daily megavoltage computed tomography imaging makes it possible to calculate daily and accumulated dose-volume histograms. Significant dose variations were observed as result of interfractional anatomic changes. These techniques enable the implementation of dose-adaptive radiotherapy.

Transoral resection of thyroid cancer metastasis to lateral retropharyngeal nodes.

BACKGROUND: Lymph node metastasis from differentiated thyroid carcinoma may occur outside of the basins at greatest risk of spread, such as the lateral retropharyngeal lymph nodes. The extensive surgery of traditional approaches to the retropharyngeal space are rarely justified in the treatment of metastatic differentiated thyroid cancer. Therefore, a less invasive surgical approach is advantageous in resection of metastatic lateral retropharyngeal nodes. METHODS: To assess feasibility and safety, we report transoral excision guided by preoperative ultrasonography in a series of 3 consecutive patients with differentiated thyroid cancer metastatic to the retropharyngeal space. RESULTS: In all cases, the metastatic lateral retropharyngeal lymph node was successfully removed by transoral retropharyngotomy without complications. CONCLUSIONS: We advocate a transoral approach guided by preoperative ultrasonography for resection of differentiated thyroid cancer metastatic to the retropharyngeal lymph nodes. The approach is feasible, minimally invasive, and safe in achieving the goals in management of regionally metastatic disease.

Headpin: a serpin with endogenous and exogenous suppression of angiogenesis.

Headpin is a novel serine proteinase inhibitor (serpin) with constitutive mRNA expression in histologically normal oral mucosa but with lost or down-regulated expression in head and neck squamous cell carcinoma. Several serpin family members are similarly lost in multiple cancer types and hold tumor suppressor functions including the inhibition of angiogenesis. However, the functional significance for the loss of headpin expression in cancer is not known. Using immunohistochemical analysis of invasive squamous cell carcinoma and matched normal squamous mucosa of patient specimens, headpin expression was lost or down-regulated in the vast majority of tumor specimens. We investigated the functions of exogenous recombinant headpin and endogenously expressed headpin related to angiogenesis. In a rat corneal assay of neovascularization, recombinant headpin protein blocked in vivo angiogenesis mediated by interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF). In assays of cellular events in angiogenesis, headpin blocked the invasion, migration, and tube formation of endothelial cells. In light of our findings of nuclear subcellular localization of headpin, we investigated the expression and secretion of angiogenic factors and found reduced mRNA, protein, and promoter activities of IL-8 and VEGF. Finally, using a murine flank tumor model, headpin expression reduced growth and microvessel density in tumors derived from headpin-expressing UMSCC1 cells relative to those from vector control cells. These findings of nuclear regulatory functions of a serpin in the inhibition of angiogenesis bring new understanding to the cellular and molecular mechanisms of serpins. Therefore, this novel serpin targets diverse mechanisms against tumor angiogenesis on which to base therapeutic strategies.

BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells.

BRAK/CXCL14 is a CXC chemokine constitutively expressed at the mRNA level in certain normal tissues but absent from many established tumor cell lines and human cancers. Although multiple investigators cloned BRAK, little is known regarding the physiologic function of BRAK or the reason for decreased expression in cancer. To understand the possible significance associated with loss of BRAK mRNA in tumors, we examined the pattern of BRAK protein expression in normal and tumor specimens from patients with squamous cell carcinoma (SCC) of the tongue and used recombinant BRAK (rBRAK) to investigate potential biological functions. Using a peptide-specific antiserum, abundant expression of BRAK protein was found in suprabasal layers of normal tongue mucosa but consistently was absent in tongue SCC. Consistent with previous in situ mRNA studies, BRAK protein also was expressed strongly by stromal cells adjacent to tumors. In the rat corneal micropocket assay, BRAK was a potent inhibitor of in vivo angiogenesis stimulated by multiple angiogenic factors, including interleukin 8, basic fibroblast growth factor, and vascular endothelial growth factor. In vitro, rBRAK blocked endothelial cell chemotaxis at concentrations as low as 1 nmol/L, suggesting this was a major mechanism for angiogenesis inhibition. Although only low affinity receptors for BRAK could be found on endothelial cells, human immature monocyte-derived dendritic cells (iDCs) bound rBRAK with high affinity (i.e., K(d), approximately 2 nmol/L). Furthermore, rBRAK was chemotactic for iDCs at concentrations ranging from 1 to 10 nmol/L. Our findings support a hypothesis that loss of BRAK expression from tumors may facilitate neovascularization and possibly contributes to immunologic escape.

Severely resorbed mandible: predictable reconstruction with soft tissue matrix expansion (tent pole) grafts.

PURPOSE: Attempts to reconstruct the severely resorbed mandible (or=3 years). CONCLUSIONS: The novel strategy of this surgery whereby bone grafts consolidate and maintain their volume by dental implants that creates a tenting effect offers predictable long-term reconstruction of the severely resorbed mandible without the complications observed with other approaches.